Implantable drug pumps and refill devices therefor

ABSTRACT

A system for refilling the drug reservoir of an implanted drug pump device may facilitate wireless data exchange between the refill system and the implanted device, e.g., to verify proper drug selection prior to commencement of the refill process. Via the wireless link, the drug pump device and refill system can exchange data such as, for example, refill information (including, e.g., a type of drug), a drug pump device history, a drug dosage log, and/or a drug-delivery protocol. Further, the refill system can facilitate reprogramming the implanted device wirelessly.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application claims priority to and the benefit of U.S. ProvisionalPatent Application No. 61/541,723, filed on Sep. 30, 2011, and isContinuation-in-Part of U.S. patent application Ser. No. 13/419,968,filed on Mar. 14, 2012, which claims priority to U.S. Provisional PatentApplication No. 61/452,399, filed on Mar. 14, 2011. The entiredisclosures of all applications are hereby incorporated herein byreference.

BACKGROUND

Medical treatment often requires the administration of a therapeuticagent to a particular part of a patient's body. Some maladies, however,are difficult to treat with currently available therapies and/or requireadministration of drugs to anatomical regions which are difficult toaccess. A patient's eye is a prime example of a difficult-to-reachanatomical region, and conventional approaches to treating manyvision-threatening diseases, including retinitis pigmentosa, age-relatedmacular degeneration (AMD), diabetic retinopathy, and glaucoma, haveassociated complications. For example, oral medications can havesystemic side effects; topical applications may sting and engender poorpatient compliance; injections generally require a medical visit, can bepainful, and risk infection; and sustained-release implants musttypically be removed after their supply is exhausted. Another example isthe chemotherapeutic treatment of cancer, such as breast cancer ormeningiomas, which often requires large doses of highly toxicchemotherapeutic agents, such as rapamycin, bevacizumab (e.g., AVASTIN),or irinotecan (CPT-11), to be administered to the patient intravenously,which may result in numerous undesired side effects outside the targetedarea.

Implantable drug-delivery devices with refillable drug reservoirsaddress and overcome many of the problems associated with conventionaldrug-delivery modalities. They generally facilitate controlled deliveryof pharmaceutical solutions to a specified target, and, as the contentsof the drug reservoir deplete, allow a physician to refill the reservoirin situ, i.e., while leaving the device implanted within the patient'sbody. The administration and maintenance benefits that such pump devicesafford, however, can also create new or increased hazards to thepatient. Care must be taken to prevent the pump from being refilled withthe wrong drug (e.g., a drug with the wrong active ingredient or anon-proprietary formulation), for example. Typically, the refill drugshould match the previously administered drug. In addition, refillingthe implanted drug pump device often entails a need to reprogram thedevice, e.g., to adjust a dosage protocol in response to a change in thepatient's condition; this step may be overlooked or mishandled.

It would be desirable, therefore, to ensure that refill of implanteddrug pump devices is accomplished in a manner that automaticallyverifies proper drug selection and that, further, ensures proper andconvenient entry of program and/or information updates to the implanteddevices during the course of the refill procedure.

SUMMARY

In various embodiments, the present invention relates to implantabledrug pump devices and systems for refilling them and facilities forestablishing communication between the refill system and the implanteddevice. The refill system generally includes a needle insertable into afill port of the implanted device and fluidically connectable to a drugcartridge or similar container, a pump for causing fluid flow from thecartridge into the drug reservoir of the implanted device, electroniccircuitry for controlling pump operation, and a communication modulethat facilitates wireless communication between the electronic circuitryand the implanted device. In some embodiments, the communication moduleis provided in a handheld telemetry wand connected to a base unit of therefill system. Via the wireless link, the drug pump device and refillsystem can exchange data such as, for example, refill information(including, e.g., a type of drug), a drug pump device history, a drugdosage log, and/or a drug-delivery protocol. Further, the refill systemcan facilitate reprogramming the implanted device wirelessly.

The refill system may also be able to electronically read an optical ID,barcode, RFID “tag,” or other electronically or optically readable labelon the drug cartridge that indicates the drug stored therein. (The term“electronically reading,” as used herein, means that the label isinterrogated automatically by an electric, magnetic, optical, or othersuitable type of sensor, and the signal acquired thereby iselectronically processed to infer the drug type (or other encodedinformation). Thus, “electronically reading” does not limit the initialinformation-acquisition process to electronic modalities, but merelyindicates that electronic data processing is used in the overall processof obtaining and utilizing information from the label. The label may,for example, be scanned by an optical sensor, and the optical signal maythereafter be converted into an electronic signal.) Using theinformation from the label, in conjunction with an indication of therefill drug required by the drug pump device (which may, e.g., be thesame drug as was previously administered by the device), the refillsystem can automatically ensure that the proper drug is being injected.In some embodiments, the refill system also provides a communicationlink to an external server, where data for many patients and implanteddevices may be aggregated—e.g., in association with the serial numbersof the respective devices—for individualized retrieval (to facilitateproper treatment of a particular patient) or for analysis across apatient population. Such central data storage provides the flexibilityto refill and reprogram the drug pump device with any refill system inaccordance herewith, as long as communication with the central servercan be established.

Accordingly, in one aspect, the invention provides a system for fillingan implanted, refillable drug pump device including a drug reservoirwith a fill port. The system includes a needle for insertion into thefill port of the drug pump device and fluidically connectable to one ormore fluid containers, one or more pumps for causing fluid flow throughthe needle between the fluid container(s) and the drug reservoir,electronic circuitry including a processor for controlling operation ofthe pump(s), and a wireless communication module facilitating wirelessdata exchange between the electronic circuitry and the implanted drugpump device. The system may further include tubing for fluidicallyconnecting the fluid container(s) to the needle.

In some embodiments, the wireless communication module is integrated inthe electronic circuitry. In alternative embodiments, the wirelesscommunication module is integrated in a handheld telemetry wand orpatient-worn eyeglasses in communication with the electronic circuitry.The electronic circuitry may be configured to control pump operationbased, at least in part, on data received from the implanted drug pumpdevice via the wireless communication module. The data may include, forexample, sensor readings of sensors disposed in the drug reservoir,information indicative of a type of drug to be administered, and/orinformation indicative of an error condition that has occurred in thedrug pump device since a previous communication between the electroniccircuitry and the drug pump device. The electronic circuitry may also beconfigured to control pump operation based, at least in part, on sensorreadings of sensors disposed in the needle, the pump(s), and/or afluidic connection between the needle and the fluid container(s).

In some embodiments, the wireless communication module is configured tosend refill information to the implanted drug pump device for storagetherein, and/or to retrieve refill information previously stored in theimplanted drug pump device. Operation of the drug pump device may bebased, at least in part, on the refill information. The refillinformation may include, e.g., a type of drug, an amount of drug, adosing schedule, or a refill date.

The one or more fluid containers may include a drug-containing cartridgeand, in some embodiments, further a waste-fluid receptacle and/or arinsing-fluid-containing cartridge. The drug-containing cartridge mayhave a label—e.g., in the form of a barcode, an RFID, an optical ID, oran EPROM—indicative of a type of drug contained in the cartridge. Therefill system may include a reader for reading the label. Alternativelyor additionally, the drug-containing cartridge may have a shapeindicative of a type of drug contained in the cartridge. In someembodiments, the electronic circuitry activates the pump to cause fluidflow from the drug-containing cartridge to the drug reservoir only ifthe type of drug indicated by the label matches a type of drug to beadministered as determined based on data received from the implanteddrug pump device via the wireless communication module.

In some embodiments, the electronic circuitry of the refill system alsofacilitates data exchange with an external server. The data exchangedwith the external server may, e.g., include a serial number of theimplanted drug pump device (as received by the system from the implanteddrug pump device via the wireless communication module) and dataassociated therewith. The data associated with the serial number of theimplanted drug pump device may include, for example, patient data, adrug dosage log, and/or a drug pump device history.

In another aspect, the invention is directed to a refill system (forfilling a drug reservoir of an implanted, refillable drug pump devicevia a fluidic connection between a drug-containing cartridge and a fillport in the drug reservoir) that includes a base unit and, incommunication therewith, a wireless communication module facilitatingwireless data exchange with the implanted drug pump device. The baseunit includes a pump for causing fluid flow through the fluidicconnection between the drug-containing cartridge and the drug reservoir,and electronic circuitry (including a processor) for controllingoperation of the pump.

In yet another aspect, the invention provides a method of verifyingproper selection of a drug prior to injection of the drug by a refillsystem into the drug reservoir of an implanted drug pump device. Themethod involves receiving a drug cartridge having an electronicallyreadable label indicative of a drug contained therein in a well of therefill system, causing the refill system to electronically read thelabel, causing the refill system to receive (from the implanted drugpump device via a wireless communication module of the refill system)data indicative of a drug to be administered, and causing the refillsystem to determine whether the drug indicated by the label matches thedrug to be administered. If so, the refill system injects the drug intothe reservoir.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing will be more readily understood from the followingdetailed description of the invention, in particular, when taken inconjunction with the drawings, in which:

FIG. 1 is a side view of an implantable, refillable drug pump device inaccordance with various embodiments of the invention;

FIGS. 2A-2H are side views of refill ports in accordance with variousembodiments of the invention;

FIG. 3 is a schematic diagram of a refill system in accordance withvarious embodiments of the invention;

FIGS. 4A and 4B are isometric views of a refill tool and tubing set,respectively, of a refill system in accordance with various embodimentsof the invention;

FIG. 5 is a block diagram of a drug pump device and refill system inaccordance with various embodiments of the invention, illustratingcommunication links between various components of the system;

FIG. 6 is an isometric view illustrating insertion of a refill needleinto the human eye in accordance with various embodiments of theinvention;

FIGS. 7A-7G are side views of refill ports with integrated mechanism forsensing needle insertion in accordance with various embodiments of theinvention; and

FIGS. 8A and 8B are side views of two side-by-side ports and adual-septum port, respectively, for facilitating refill of the drugreservoir and simultaneous pressure balancing through access to an outerchamber of the drug pump device, in accordance with various embodimentsof the invention.

DETAILED DESCRIPTION

The present invention relates, generally, to implantable drug pumpdevices with refillable drug reservoirs, as well as to apparatus,systems, and methods that facilitate the refill process. Variousembodiments described herein relate specifically to drug pump devicesimplanted into the eye (e.g., between the sclera and conjunctiva);however, many features relevant to such ophthalmic pumps are alsoapplicable to other drug pump devices, such as, e.g., implantableinsulin pumps. Accordingly, where reference to the eye is made in thefollowing description, or in the figures, such reference is generallyintended to be merely illustrative, and not as limiting the scope of theinvention.

FIG. 1 illustrates an exemplary electrolytically driven drug pump device100 in accordance herewith (described in detail in U.S. patentapplication Ser. No. 12/463,251, the entire disclosure of which ishereby incorporated by reference). The drug pump device 100 includes acannula 102 and a pair of chambers 104, 106 bounded by an envelope 108.The top chamber 104 defines a drug reservoir that contains the drug tobe administered in liquid form, and the bottom chamber 106 contains aliquid which, when subjected to electrolysis using electrolysiselectrodes 110, evolves a gaseous product. The two chambers areseparated by a corrugated diaphragm 112. The cannula 102 connects thetop drug chamber 104 with a check valve 114 inserted at the site ofadministration. The envelope 108 resides within a shaped protectiveshell 116 made of a flexible material (e.g., a bladder or collapsiblechamber) or a relatively rigid biocompatible material (e.g.,medical-grade polypropylene). Control circuitry 118, a battery 120, andan induction coil 122 for power and data transmission are embeddedbetween the bottom wall of the electrolyte chamber 106 and the floor ofthe shell 116. Depending on the complexity of the control functionalityit provides, the control circuitry 118 may be implemented, e.g., in theform of analog circuits, digital integrated circuits (such as, e.g.,microcontrollers), or programmable logic devices. In some embodiments,the control circuitry 118 includes a microprocessor and associatedmemory for implementing complex drug-delivery protocols. The drug pumpdevice 100 may also include various sensors (e.g., pressure and flowsensors) for monitoring the status and operation of the various devicecomponents, and such data may be logged in the memory for subsequentretrieval and review.

Implantable, refillable drug pump devices need not, of course, have theparticular configuration depicted in FIG. 1. Various modifications arepossible, including, e.g., devices in which the drug reservoir and pumpchamber are arranged side-by-side (rather than one above the other),and/or in which pressure generated in the pump chamber is exerted on thedrug reservoir via a piston (rather than by a flexible diaphragm).Furthermore, the pump need not in all embodiments be drivenelectrolytically, but may exploit, e.g., osmotic or electroosmotic drivemechanisms, or even pressure generated manually.

Importantly for the prolonged use of the drug pump device 100 followingimplantation, the device 100 includes one or more ports 124 in fluidcommunication with the drug reservoir 104, which permit a refill needle(not shown) to be inserted therethrough. The refill port 124 may definean aperture through the wall of the reservoir 104, which may be closedand sealed with a septum or plug made of a puncturable, self-sealingmaterial, allowing a non-coring needle (e.g., a needle that does notremove any of the material it punctures) to pierce through the septumwhile ensuring that the septum reseals itself, or “heals,” upon removalof the needle. Preferably, the self-sealing material is biocompatibleand able to withstand multiple punctures by the needle. The septum orplug may be made of any of a variety of elastomeric polymers (such as,e.g., silicone, polydimethylsiloxane (PDMS), polyurethane, polyethylene,parylene C, or rubber), and the specific composition of the polymermixtures may be chosen so as to enhance the self-sealing properties.Silicone, for example, is naturally self-healing, but this property ismore pronounced in particular formulations well-known to persons ofskill in the art. The septum material may be injected directly into theaperture of the port and cured in place. In some embodiments, a slit ispre-formed in the septum, and the needle is inserted along this slit;the septum and surrounding port walls are sized such that radialpressure from the walls of the port compresses the septum and, with it,the slit, preventing leakage during filling and after the needle hasbeen removed.

FIGS. 2A and 2B provide close-up views of a simple refill port 200before and after, respectively, insertion of the needle 202. As shown,the septum 204 need only partially extend through the aperture 206 inthe reservoir wall 208, and may form a single block of material withflat needle entry and exit surfaces 210, 212. FIGS. 2C-2F illustratevarious alternative refill port embodiments. For example, the port shownin FIG. 2C includes a needle stop 220 protruding from the side wall ofthe port at a lower end. Once the needle 202 is inserted sufficientlyfar to inject fluid into the drug reservoir 104, the needle stop 220halts further progress of the needle to avoid accidental damage to thedrug pump device 100 and/or the patient. FIG. 2D illustrates a port witha conically shaped recess 230 at the entry side merging into a narrowchannel portion 232, which collectively serve to guide the needle 202through the port along a central axis 234. As illustrated in FIG. 2E,the aperture through the reservoir wall 208 need not open directly intothe main portion of the drug reservoir 104. Instead, it may open into aport chamber 236 that is fluidically connected to the reservoir 104,e.g., via a fluid channel perpendicular to the needle entry direction.In this embodiment, the bottom wall of the port chamber 236 serves tostop the needle.

Finally, FIG. 2F shows an embodiment in which the septum 240 includesprotuberances 242, or “bumps,” on the needle entry and exit surfaces244, 246, located around the desired puncture sites. These bumps serveto direct pressure exerted at the exit surface 246 (i.e., the interiorsurface of the reservoir 104) by the liquid drug and at the entrysurface 244 by the ambient fluid (e.g., of the surrounding tissue)toward the needle puncture path 248 (i.e., the straight line connectingthe desired puncture sites and corresponding to the desired insertionpath of the needle). Pressure thus redirected can aid in theself-healing of the septum 240. As shown, the bumps 242 may takesubstantially semi-spherical form; however, other shapes may also beused to redirect pressure and promote self-healing. Further, the septum240 need not necessarily have bumps 242 on both sides. FIG. 2F furtherillustrates use of a separate layer 250 of non-puncturable, flexiblematerial disposed above the aperture through the reservoir wall. Thelayer 250 has a hole 252 centered above the bumps 242, which serves toguide the needle toward and along the desired insertion path 248. Thehole 252 is originally smaller than the cross-section of the needle, butincreases in size as pressure exerted by the needle deflects the layer250 downward, as indicated in the figure by dashed lines. The variousfeatures of the refill port may, of course, be used in differentcombinations. Further embodiments are described, for example, in U.S.patent application Ser. No. 12/463,247, the entire disclosure of whichis hereby incorporated by reference.

The ports shown in FIGS. 2A-2F are configured for substantiallyperpendicular needle insertion. In certain alternative embodiments,however, the refill port 124 is angled with respect to the reservoirwall, both to minimize pain and vitreal reflux and to improveself-healing. Oblique needle-entry paths through the septum can enhanceself-sealing performance because, after removal of the needle, externalpressure exerted on the septum from both sides acts at an angle to theneedle tunnel, tending to collapse it and render its diameter smallerthan that of the needle. Orienting the refill port so that needle entryoccurs at an angle to the pressure developed by the pump can thereforeincrease the reliability of the plug or septum in a similar manner asthe bumps describe above with respect to FIG. 2F.

Various other arrangements can be used to exploit pressure generated inthe drug reservoir 104 (in particular, when the pump device activelypumps) to aid self-healing. In one embodiment, the entry path for theneedle remains perpendicular to the surface, but the inside of therefill port is configured so that part of a side of the refill septum isalso exposed to pump pressure in order to close any holes through theseptum. In another configuration, the septum is larger at the bottomthan at the top, and mounted so as to be wedged in a conical bore. Thepressure of the pump acts to push the septum up into the bore, resultingin compression of the refill needle holes. The conical shape of therefill port septum also accommodates inaccuracy in the angle of needleinsertion. In still another embodiment, the refill plug or septum isconfigured as a membrane that covers and extends beyond the perimeter ofthe bore through the reservoir wall. The edges of the septum are bondedto the wall or held with corrugations, with the septum initially convextowards the inside of the bore. When the pump is activated, the pressureacts to push the bulging septum into its containing area, creatinglateral pressure that closes any needle holes in the septum. In anotherdesign, the bottom of the septum is convex so that pressure conductedinto the bore compresses the septum therein, creating lateral pressurethat acts to further close the holes. Still another design initiallyplaces and maintains the septum under lateral compression, creating acontinual closing pressure on any needle paths through the thickness.

In yet another embodiment, shown in FIGS. 2G and 2H before and afterneedle insertion, respectively, the needle port 260 is configured so asto entirely avoid the need to pierce the septum or plug 262. Instead,the plug 262 is pushed by a blunt tip needle 264 with an aperture 266(or “port”) in the side wall of the needle tip. When pushed, the plug262 collapses and clears a fluidic path 268 leading to the drugreservoir 104. When the needle 264 is retracted back, releasing thepressure on the silicone plug 262, the plug 262 returns to its initialshape, closing the fluidic path 268 to the reservoir 104. The plug 262is typically made of silicone, and may have a convex (viewed from theneedle), inverted-bowl shape. The needle 264 is sealed by a siliconeO-ring 270 (or, more generally, a second elastomeric septum with acenter hole) disposed above the plug 262 to block the leak path of fluidto the outside of the refill port 260. (The O-ring 270 may have, in itsuncompressed state, an inner diameter slightly below the needlediameter.) The deformable plug 262 may have a hard, needle-impenetrableplate 272 attached thereto at an upper surface; this hard plate 272transfers pressure exerted by the needle so as to collapse the plug 262.(Alternatively, the plate may simply be disposed above the plug, withoutbeing attached.) The needle port 260 may include a wall structure 274that is molded or machined into a complex shape defining a layeredcavity that accommodates the deformable septum 262 and O-ring 270. Theport may also include a guiding disk 276 forming a conical aperture,similar to that shown in FIG. 2D, for guiding the needle 264.

The design of needle port 260 is beneficial in several ways: Since theneedle 264 never penetrates the septum 262, the needle 264 need not benon-coring, allowing for larger needle diameters, which, in turn,facilitate more rapid filling of the reservoir 104. Further, there isloose particle rapid fill. Only minimum insertion force is needed, and alarger initial target for the needle prior to penetration is provided.

Through the refill port 124, the existing fluid in the reservoir (suchas any residual drug) can be removed, the reservoir washed, and afilling/refilling solution injected. Certain embodiments of theinvention involve an external refill system that can be interfaced tothe drug reservoir for the automatic filling/refilling of the reservoir,as conceptually illustrated in FIG. 3. The refill system 300 generallyincludes at least two channels: one channel 302 for aspirating fluid(e.g., expired and/or remnant drug) from the reservoir of the drug pumpdevice 100 and another channel 304 for loading new drug into thereservoir. In some embodiments, the system further includes a thirdchannel 306 for rinsing the drug pump prior to filling it with the freshdrug. Each channel is fluidically connectable to a depot or container,e.g., one containing the drug to be dispensed (308), one receiving wasteliquid from the drug pump device 100 (310), and one containing therinsing solution (312). This rinsing solution may be the drug vehicle(e.g., a fluid missing the active ingredient, but otherwise having thesame composition as the liquid drug), or any solution compatible withthe drug and drug pump device 100.

The refill system 300 also includes one or more pumps 314 for generatingpositive or negative pressure to effect the infusion and suction ofliquid into and out of the drug pump device 100. The pumps 314 may bestandard mechanical pumps (e.g., gear, diaphragm, peristaltic, orsyringe pumps), or pneumatic systems such as, e.g., vacuum generators,air compressors, pneumatic motors, pneumatic actuators, etc. In someembodiments, pressure sensors, flow sensors, and/or valves areintegrated into the channels 302, 304, 306 and/or the pumps 314 tofacilitate monitoring of the flow rate and/or pressure during therefilling process and controlling pump operation based thereon. Therefill system 300 further includes electronic control circuitry 316 thatdirects the operation of the pump(s), and/or a user interface 318 thatallows a user (e.g., a physician or nurse) to provide input to thecontrol circuitry 316 and/or to manually trigger certain pre-definedpump functions (e.g., via buttons, a foot pedal, and/or a conventionalcomputer user interface including, e.g., a screen, keyboard, and mouse).The electronic control circuitry is conventional and typically comprisesa processor for performing computations related to the pump operation.The processor may be a general-purpose or special-purpose processor, andmay utilize any of a wide variety of data-processing and controltechnologies, including, e.g., a microcomputer, mini-computer, mainframecomputer, programmed microprocessor, microcontroller, peripheralintegrated circuit element, CSIC (customer-specific integrated circuit),ASIC (application-specific integrated circuit), logic circuit, digitalsignal processor, programmable logic device such as an FPGA(field-programmable gate array) or PLA (programmable logic array), RFIDprocessor, or smart chip.

The refill system 300 may be implemented as a single unit or,alternatively, as multiple components. In certain embodiments, the pumps314, control circuitry 316, and (optionally) valves and sensors areintegrated into a reusable base unit, whereas the fluid channels 302,304, 306 are provided in a replaceable and/or disposable tubing setconnectable to the base unit and, at the other end, to a refill needle.The needle is preferably a small-bore needle and may, as shown in FIG.4A, be integrated into a handheld refill tool 400 including an ergonomichandle portion 402 with a push button, slider, or other mechanicallyactuable control 404 for extending and/or retracting the needle 406. Therefill tool 400 allows a physician to refill the implanted device insitu. In preferred embodiments, the same needle is used during theentire refill process so as to minimize the needle insertion frequencyinto the drug reservoir and the associated stress for patient andphysician as well as the wear on the refill port. A single needleinsertion may even suffice if multiple fluids (e.g., multiple separatelystored drugs to be administered together) are to be injected into thedrug pump device 100. The needle 406 is, thus, sequentially connected todifferent fluid containers.

FIG. 4B illustrates an exemplary two-channel tubing set 450 suitable forthis purpose. The tubing set 450 branches, from a proximal channelportion 452 connected to the needle 406, into two channels 454, 456coupled at the distal end, via respective fluidic connectors 458, 460,to the containers providing fluid to or receiving fluid from thereservoir 104 of the implanted device 100. The channels 454, 456 mayhave one-way valves that allow drug or rinsing fluid from containers308, 312 to flow via the refill channel 454 to the needle 406 and wastefluid from the reservoir 104 to flow via the aspiration channel 456 tothe waste-fluid container 310, but prevent fluid flow in the respectiveopposite direction. Further, the channels 454, 456 may include sterilefilters 462 that prevent air from entering and contaminating the newdrug. The same types of filters may also serve to prevent fluid fromaccidentally entering a vacuum pump, coming into contact with sensors orelectronics within the base unit, or otherwise contaminating the drugrefill system 300 (e.g., by means of a hydrophobic membrane that allowspassage of air, but not an aqueous solution). As a person of skill inthe art will readily appreciate, the tubing set 450 can be modifiedstraightforwardly into a three-channel fluidic manifold.

In some embodiments, one or more of the containers 308, 310, 312 holdingthe drug, waste liquid, and rinsing solution are provided in the form ofvials or cartridges (hereinafter used synonymously), and may be soldalong with the disposable tubing set 450 in a drug refill kit. Thewaste-liquid cartridge 310 (or other container) may contain a dye thatchanges the color of the waste liquid upon contact to a noxious or atleast noticeably anomalous hue such as black so as to prevent users frominadvertently re-injecting waste drug back into the patient or pump. Thedye may, e.g., consist of natural or synthetic dyestuffs that arecontained in the cartridge in powder form or line the surface of thecartridge. Furthermore, the cartridge 310 may contain reactive agentsthat disable use of the drug by destroying its activity, e.g., via anacid-base reaction, but which are non-toxic so as to avoid harm to thepatient should the mixture be re-injected.

The base unit or refill tool of the refill system 300 may have receivingwells or other receptacles for the cartridges 308, 310, 312. In certainembodiments, the cartridges have a proprietary shape that must mate witha complementary receiving well in the refill system. This approach canalso facilitate mechanical locking of the cartridge to the drug refillsystem, e.g., so that it snaps into place. Mechanical locking may beaccomplished, e.g., using a trapezoid, triangle, or hexagonal maleconnector on the drug refill system and a geometrically complementaryconnector on the cartridge. Using cartridges of a particular shape inconjunction with matching receiving wells may serve to preventnon-proprietary cartridges or drugs from being used with the refillsystem 300, e.g., to ensure the integrity of the drug. A further levelof security may be obtained by facilitating electronic communicationbetween the cartridge and the refill system 300. For example, thecartridge may have a barcode encoding the identity of the drug therein,and the refill system 300 may be equipped to read the barcode once thecartridge is introduced. Alternatively, the cartridge may have anoptical, RF, or similar ID tag or other electronic information storage(e.g., a ROM or an EPROM) that specifies the contents of the cartridge,and which is interrogated by the refill system 300.

In various embodiments, the refill system 300 facilitates wirelesscommunication with the drug pump device 100. For example, the controlcircuitry 316 of the base unit may include a radio-frequency (RF)transceiver or similar component that exchanges data with the inductioncoil 122 embedded in the pump device 100. In some embodiments,illustrated in block-diagram form in FIG. 5, a communication ortelemetry module 500 (including a transceiver and related circuitry) isprovided separately from the control circuitry 316, e.g., in a handheldtelemetry wand 502 that allows the operator (e.g., a nurse or physician)to conveniently bring the wand in the vicinity of the implanted pumpdevice 100, thereby reducing power requirements on the device 100 and,consequently, its footprint. The wand may be corded to the base unit, orcommunicate with the base unit via a separate wireless connection. Insome embodiments, special eyeglasses 504 equipped with a telemetrymodule 506 are used to recharge the pump's battery 120 via the inductioncoil 122; such eyeglasses are described in U.S. Ser. No. 12/463,251,filed on May 8, 2009, the entire disclosure of which is herebyincorporated by reference. These eyeglasses 504 and the refill system300 may be connected to each other or to a common console, and wirelessdata exchange with the drug pump device 100 may occur via the eyeglassesrather than a separate telemetry wand 502.

Via the telemetry module (of the telemetry wand 502 or the eyeglasses504), the base unit may send refill information, including, e.g., thetype of drug, the volume injected into the reservoir, a drug dosingschedule, and the date of refill, to the pump device 100. The drug pumpdevice 100 may store this information in its on-board memory, preferablyin encrypted form to ensure patient privacy, and may provide it whenlater interrogated by the refill system or other wireless device. Theprevious refill information may be used to ensure that the refilldrug—as determined by the refill system's electronic label reader 508from the barcode, RFID, optical ID, EPROM, or other electronic label 510of the cartridge, or from the proprietary shape of the cartridge—matchesthe previously administered drug, thereby preventing off-label or otherimproper uses of the pump. Alternatively or additionally, the pumpdevice 100 may be programmed to accept only a particular drug, and whenwireless communication is established between the refill system 300 andthe pump device 100, the refill system 300 and the pump exchangeinformation to ensure that the refill drug matches the drug for whichthe pump was programmed. In either embodiment, refill isprevented—typically by disabling operation of the refill system—if amatch is not registered. Of course, it may sometimes be necessary ordesirable to change the drug administered to the patient, e.g., if apreviously used drug caused complications. In this case, the operatormay override the control signal that prevents the refill from commencingand/or reprogram the drug pump device 100 for the new drug.

The identity of the drug can also determine or limit the rate at whichthe pump dispenses the drug, or otherwise influence drug delivery by theimplanted device 100. For example, in some embodiments, the drug pumpdevice 100 is pre-programmed with different drug delivery protocols fortwo or more respective drugs (or, alternatively, with a generic drugdelivery protocol including one or more variable parameters whose valuesdepend on the type of drug to be administered). Based on the drugidentified in the refill information, the drug pump device then selectsone of the delivery protocols for execution. This functionalityfacilitates, e.g., easy testing of multiple alternative treatment agentsfor a particular disease, which may require different drug dosages,delivery intervals, etc., without necessitating re-programming of thedrug pump device 100 when the treating physician decides to switch fromone of the drugs to another.

The communication link established between the drug pump device 100 andthe refill system 300 may also be used to download a stored drug dosinglog or the pump operation history (including, e.g., information aboutany error conditions that have occurred in the pump device 100 since theprevious communication) from the drug pump device 100. This informationmay be displayed on a screen (e.g., of a computer console that is partof the user interface 318) prior to commencement of the refillprocedure, enabling the physician to detect any problems with theoperation of the device 100 and relate the patient's condition to drugadministration over extended periods of time. The physician may, forexample, have the option to display twelve months of pump history or tenyears of drug delivery history. Further, the physician may reprogram thedrug pump device 100 at the time of refill, e.g., to adjust dosageprotocols in response to changes in the patient's condition or newinsights derived from medical research. In some embodiments,communication between the drug pump device 100 and the refill system 300is sustained during the refill procedure to facilitate monitoring theprocess based on sensor readings acquired in the pump device 100. Forexample, sensors may continuously measure the pressure and fill stage ofthe drug reservoir 104, and send this data to the refill system 300,where it provides feedback to the processor of the control circuitry 316and/or a physician manually controlling the refill system 300.

The data exchanged with the drug pump device 100 may be stored on alocal server 515 integrated with or connected to the drug refill system300. Alternatively, the communication module may permit the refillsystem 300 to communicate with an external server 520, e.g., remotelyvia the Internet. For example, the refill system 300 may have Wi-Fi,Zigbee, or a cellular phone chip (GSM, CDMA) that is constantlyactivated to cellular service or other wireless capability. This permitspatient and drug data to be stored outside the refill system 300 (“inthe cloud”), and may provide further levels of security and operationalflexibility. Centralized information storage not only simplifiesconstruction of the refill system 300 (e.g., by eliminating the need fora local server or for security systems required to comply with patientprivacy regulations in case of local storage of patient data), butallows a particular patient's implanted pump to be interrogated andrefilled by any refill system in any location, so long as communicationwith a remote central server can be established. Because the centralserver will have substantial storage capacity and, in variousembodiments, the ability to autonomously query outside resources such asdrug-interaction tables and manufacturer's information, levels of safetybeyond drug matching may be implemented. Further, a central database maymaintain (or link to) patient records and include database recordsassociating the serial number of each implanted drug pump device 100with the identity of the patient who received it. When the refill system300 obtains the pump serial number through wireless communication withthe pump device 100 and the identity of the drug in a newly insertedcartridge, it may communicate this information to the central server,which not only verifies the match but also reviews patient records toensure that the drug and dosage remain appropriate for the patient(e.g., in light of additional drugs prescribed for the patient since thelast pump refill).

Wireless communication between the pump and the refill system ispreferably encrypted. The wireless circuitry is typically near-field andmay utilize any suitable communication protocol, e.g., Bluetooth,Zigbee, or IrDa. Wireless communication between the refill system andthe Internet, on the other hand, may take place via near-field orfar-field wireless infrastructure. In some embodiments, the refillsystem establishes communication with the server via a wireless gatewayserving the site where the system is used (and implementing, forexample, the Wi-Fi protocol or another variant of the IEEE 802.11standards). In other embodiments, a cellphone (e.g., GSM) chip isinstalled in the refill system 300, either as a primary communicationsplatform or as a backup, should local wireless access prove unavailable.Of course, the refill system 300 may also communicate with the Internetthrough a wired connection (such as via Ethernet cables).

The refill system 300 is typically prepared for use by introducing adrug-containing cartridge into the base unit or the hand-held refilltool 400 and establishing fluid communication between the cartridge andthe outflow needle 406. The physician then manipulates the refill tool400 to insert the needle into the drug reservoir 104 of the implanteddevice 100 via the fill port 124, as shown in FIG. 6. Various visualaids and sensing mechanisms may be integrated into the port 124 and/orthe refill tool to aid the physician in locating the port 124 to protectthe patient from inadvertent punctures by the needle, as well as toverify proper needle insertion before the refill pumps are activated.

In some embodiments, the needle entry port 124 is identified by means ofa visualization ring surrounding the port aperture; variousimplementations of such a ring are described in U.S. patent applicationSer. No. 12/348,178, the entire disclosure of which is herebyincorporated herein by reference. The visualization ring may include,for example, fluorescent pigments (e.g., excited by ultravioletradiation), a light emitting diode, or a material that enhances surfaceechogenicity and acoustic shadowing. For example, if the refill portseptum is made of silicone while the surrounding reservoir wall orrefill port housing is made of a detectably different material, anultrasonic probe may be incorporated into the refill tool to detect whenthe tool is located over the refill port septum. If the refill porthousing is ultrasonically highly reflective, this probe can use thesimple absence of ultrasonic reflection to detect the “hole”constituting the refill septum. Electronics may also be present in thedrug-delivery device in order to move or vibrate the visualization ringso as to provide mechanical feedback to the physician regarding thelocation of the port 124. In other embodiments, the visualization ringincludes a magnetic material or a coil generating a magnetic field thatcan be detected by a magnetic-field sensor integrated into the refilltool. Still other modalities to facilitate visualization of the refillport include optical coherence tomography and capacitive sensing. Morethan one modality may be employed for patients who form excessivelyfibrotic encapsulation around the implanted pump device 100, impedingvisual identification.

The visualization ring (or the pump device itself) may be illuminated,in some embodiments, using a “transillumination” light source. Inophthalmic applications, the light source is typically held against thepatient's eye. The light emitted by the light source may have a red,infrared (IR), or other wavelength (or wavelength band) optimized forpenetrating the conjunctiva, or may be an excitation light for aphotoluminescent material in the visualization ring and/or the pump. Oneapproach is to use a stand-alone light source, e.g., a manipulablegooseneck lamp or one that the clinician may wear on his forehead. Inanother approach, the light source is integrated with the handheldrefill tool that contains the refill needle, ensuring proper alignmentbetween the light source and the needle, or combined with a tool to holdor grasp the pump device or other manipulator (leaving the surgeon'sother hand free to fill the implant). For example, the procedure forrefilling the pump may call for offsetting the conjunctiva over therefill port prior to needle insertion (to lower the chance of infection)and stabilizing the pump device and surrounding tissue during the needleinsertion and refill process; a light can be combined or integrated witha suitable manipulator tool for offsetting the conjunctiva andstabilizing the eye. The light source can be a fiber-optic extension oran LED-based light source that has a bendable neck so that the tip ofthe flexible tube (with the light source at the end) can be placedoptimally. Depending on the placement of the pump device and thevariability of the surgeon's desired approach, a movable light sourcewith a bendable neck may be desirable in order to target the light in asafe location.

Once the proper entry site has been identified and the needle haspunctured the refill plug or septum, it is important to ensure, prior toinjecting medication, that the refill needle fully penetrates the septumand is located at the reservoir-side of the refill port. Otherwise, ifthe practitioner does not fully insert the needle into the pump refillport but instead stops short and injects the medication into bodytissue, so-called “pocket fills” can occur. Injecting highlyconcentrated medicine into the body instead of the pump device can behazardous or even fatal.

One approach to ensuring proper needle insertion, which is applicable,e.g., to ophthalmic drug pump devices, is to use IR illumination thatpenetrates the conjunctiva and an IR camera (placed outside the eye)imaging through the conjunctiva to visualize the needle as it is guided.IR radiation enables imaging the interior of the fill port 124, providedthe port housing or walls are not made of metal. Illumination may beachieved with the same types of light sources as described above in thecontext of visualizing the refill port 124 to find the correct puncturesite, including, e.g., a light source integrated into the refill tool.The IR camera images may be displayed on an IR monitor (or, optionallyafter image processing, on a general-purpose screen of the userinterface of the refill system), or in a goggle worn by the physician ora retinal display.

Visual confirmation that the refill needle has been inserted by thedesired amount (or “bottomed out”) may also be provided, as shown inFIG. 7A, by a wire 700 integrated inside the refill needle 406, whichprotrudes a certain amount from the refill tool 400 when the needle isin the proper position. Alternatively or additionally, a series of marks702 on the refill needle may be used to gauge how far the needle 406 hasbeen inserted. The needle may also have a mechanical stop of a diameterexceeding that of the aperture of the refill port, and positioned suchthat the needle is correctly positioned within the reservoir when thestop reaches the port or an overlying tissue layer (e.g., in ophthalmicapplications, the conjunctiva); exemplary stops are described, e.g., inU.S. patent application Ser. No. 12/348,178.

In another approach, one or more sensors integrated into the refill port124 and/or the refill tool 400 are used to confirm proper needleposition within the refill port. For example, a line-of-sight opticalsensor may be employed. The sensor pair includes an optical emitter(e.g., an LED) and detector (e.g., a photodiode) placed on oppositesides of the refill port 124—e.g., in simple port embodiments as shownin FIG. 2A, on opposite sides of the wall defining the port aperture,or, in port embodiments including a port chamber separate from the drugreservoir as shown in FIG. 2E, on opposite sides of the chamber wall—soas to establish a light path across the port 124; light send by theemitter and received by the detector results in an electronic signal inassociated sensor circuitry. When the needle is inserted into the refillport 124, the light path is blocked and the signal, consequently,interrupted, enabling the sensor to detect the needle. Similarly, anacoustic wave emitter and detector (operating, e.g., in the ultrasoundregime or within another frequency range) may be disposed on oppositesides of the refill port. When the needle is inserted, the acousticimpedance (as indicated by the strength of the signal from the acousticdetector) will change, facilitating needle detection.

In some embodiments, illustrated in FIG. 7B, the opticaldetector-emitter pair is not located inside the refill port 124, butinstead outside opposing optical windows 710 in the side wall of theport chamber. The windows 710 are positioned such that, when the needleis properly inserted, the optical signal path between the emitter 712and the detector 714 is interrupted at least partially, which may bedetected with suitable circuitry (as explained above). In an alternativeembodiment, one of the windows 710 is replaced with an optical reflectorplaced at the interior port chamber wall, and the detector is locatednext to the emitter outside a single window. In this case, the insertedneedle 406 blocks the light path between the emitter and reflector (and,similarly, between the reflector and detector) at least partially,reducing the reflected light measured by the detector.

In yet another embodiment, illustrated in FIG. 7C, visualization and/oroptical detection of needle insertion are achieved by integrating anoptical fiber 720 with the needle that terminates at the needle tip (or,generally, a portion of the needle that is placed inside the fill portwhen the needle bottoms out) so as to illuminate the interior walls ofthe fill port once the needle 406 has been inserted. The optical fiber720 may be attached to the exterior wall of the needle 406 and,optionally, be clad with a protective coating, or it may be providedinside the needle 406, e.g., in the second lumen of a dual-lumen needlewith a side opening for light emission. The optical signal indicative ofproper needle insertion may be captured with a suitable sensor in theport, or observed by eye, e.g., through an optical window 710 in theport wall. The sensor may also be placed on the optical window 710. Toavoid light penetrating through the septum before needle insertion, theseptum material is generally optically opaque. The interior walls of thefill port 722 may be highly reflective so as to reflect at least aportion of the light from the optical fiber to the sensor or the opticalwindow 710.

In a modified embodiment, illustrated in FIG. 7D, a luminescent (e.g.,fluorescent) material 726 is used in the needle port 124 and/or the drugreservoir 104 (e.g., applied as a coating to portions of the walls ofthe port or reservoir) in conjunction with a light source provided atthe needle tip that emits light at wavelengths inducing luminescence.For example, an optical fiber 720 integrated into the needle may beconnected to a light source external to the needle and provide light viaan exit face at the needle tip (or, generally, at a portion of theneedle that will be located inside the reservoir or port when the needleis properly positioned for refill) so as to irradiate the luminescentmaterial 726 once the needle 406 has been inserted. The luminescentsignal indicative of proper needle insertion may be captured with asuitable sensor in the port 124 or reservoir 104, or observed by eye,e.g., through an optical window in the port or reservoir wall. To filterout the original emission and ambient light, the detector or opticalwindow may be equipped with a suitable optical filter or dichroicmirror. Alternatively, all of the light may be captured by a CCD camera(e.g., placed outside the optical window), and the luminescent signalmay be separated from the background via frequency-filter algorithmsapplied during image processing.

In some embodiments, the fluorescent light can also be observed throughthe septum if, for example, the septum is transparent. If fluorescentmaterials are also used to guide needle insertion (e.g., via avisualization ring), care must be taken in the design so that lightemitted by the light source prior to insertion but passing through theseptum does not excite the fluorescent material in the reservoir evenwhen the needle is still outside the port.

In alternative embodiments, electrical or magnetic sensors are employed.For example, two electrodes can be disposed on opposite sides of therefill port to measure electrical impedance (or capacitance) betweenthem. If a needle is inserted, the impedance changes and varies withneedle position until the needle is fully inserted. Similarly, magneticor inductive position sensors that utilize one or more induction coilsin the refill port in conjunction with a ferromagnetic needle (or aneedle incorporating ferromagnetic material along a portion of itslength) may be used. The coil(s) inside the refill port may sense thepresence and, in some implementations, the position of the needle withinthe port. In one embodiment, the sensor operates in a manner analogousto a linear variable differential transformer (a common type ofelectromechanical transducer that converts rectilinear motion into acorresponding electrical signal). For example, three solenoids may beplaced end-to-end around the port aperture. An alternating currentdrives the center coil, inducing a voltage in the top and bottom coilswhen the ferromagnetic portion of the needle provides a common corelinking the solenoids. As the needle moves, the center coil's linkage tothe two neighboring coils changes and causes the induced voltages tochange. In other magnetic-sensor embodiments, as shown in FIG. 7E, coilsor permanent magnets 730 are used to create a magnetic field in theport, preferably with a locally maximum field strength along a(substantially central) axis 732 through the port (i.e., along thedesired needle insertion path). The magnets may, for example, beintegrated into the wall of the port, or the entire wall may be made of,or coated with, a magnetic material. A magnetic-field sensor 734integrated with the needle is employed to detect the region of highestfield strength, providing feedback for the guidance of the needle alongthe axis through the port. Ideally, the magnetic-field sensor 734 isprovided at the needle tip, but even if the sensor is not locatedbetween the magnets 730, it may be able to measure portions of themagnetic field generated thereby. Conversely, the field-generating coil(or permanent magnet) may be integrated into the needle (or the needlebe made of or coated with a magnetic material), and the magnetic-fieldsensors provided in the refill port.

Another way to ensure that the refill needle has fully entered the pumpdevice 100 through the refill port 124 is to use a mechanical switch atthe bottom of the refill port 124 that activates when the needle strikesit. The switch may, for example, be disposed on the bottom of a portchamber (opposite the aperture) such as the one shown in FIG. 7F, ormounted on a needle stop 220 as shown in FIG. 2C. In yet anotherembodiment, the needle is permitted to penetrate the entire interior ofthe drug reservoir 104 and stopped at the reservoir wall opposite therefill port 124, in which case the switch may be disposed on thisopposite wall. Instead of a mechanical switch, a piezo-electric element740 with associated circuitry may be used. When the (fully inserted)needle 406 exerts force against the piezo-element 740, a voltage 742 isinduced across the element, and this voltage can be measured by theassociated circuitry. Another approach, illustrated in FIG. 7G, involvesincluding the needle itself as part of an electrical circuit, e.g., byapplying a small voltage to a conductive plate 750 (e.g., of metal or aresistive material such as a conductive polymer) at the bottom of therefill port and using the needle to detect this voltage with a suitablesensor 752 upon contacting the plate 750. If the needle 406, when incontact with the conductive bottom plate 750, along with the detectioncircuitry presents an impedance less than or not excessively greaterthan that of the electrical path through the bottom plate 750, adetectable electrical current can be diverted through the needle 406.The impedance difference is not excessive so long as the measurementcircuitry can reliably detect the current. For example, in variousembodiments, the impedance ratio of the detection circuitry to theelectrical path through the bottom plate 750 is no more than 10, no morethan 100, or no more than 1000, depending on the sensitivity andcharacteristics of the detection circuitry.

In the various sensor embodiments described above, complete insertion ofthe needle generally causes creation of an electrical signal in thecircuitry associated with the sensor, which may be embedded in the drugpump device 100 and/or the refill tool. Signals generated in the pumpdevice 100 may be communicated to the refill system 300 via the wirelesslink between the pump device 100 and the telemetry wand (or eyeglasses),whereas signals measured in the refill tool may be send to the base unitof the refill system 300, e.g., via a data cable. The control circuitry316 of the base unit may condition activation of the refill pumps onreceipt of a signal indicative of proper needle insertion.

Still another way of ensuring complete entry of the needle relies on theactivation of the (e.g., electrolysis) pump of the implanted drug pumpdevice 100 to provide detectable sub-dosing pressure (e.g., pressurelower than that used during drug delivery to the patient's body) on theresidual drug in the drug reservoir 104. The refill system 300 detectsthis fluid as it is forced into the refill needle when the needle is inthe proper location within the port. For example, the refill system maydirectly detect fluid pressure in the needle or fluid flow into therefill device via a suitable pressure or flow sensor, or thepractitioner can visually observe fluid traveling into the needle and/orattached tubing. Placement of the needle in the port may thus beconfirmed prior to proceeding with the refilling procedure. Of course,this approach depends on avoiding full depletion of drug from the pumpreservoir. An alternative is to inject saline solution (which would notharm the patient if accidentally injected into tissue) into the drugreservoir 104 and then activate the pump to determine whether the fluidis forced back into the refill system. Here, too, the pump must be ableto maintain or produce sub-pumping pressure on the drug reservoir.Alternatively, the pump can be configured to operate at a very lowdosing amount and rate, such that pressure is developed, but little ifany drug (or other fluid) is dosed while the needle location isconfirmed. Yet another embodiment exploits the fact that the drugreservoir 104 is, in the natural rest state of the drug pump device 100,under a slight vacuum. Therefore, if a pressure sensor in the needle 406detects a vacuum pressure, this is indicative of fluid communicationbetween the needle and drug reservoir.

Following proper introduction of the needle into the refill port orreservoir, the refill pumps are activated to withdraw any remaining drugfluid from the reservoir, inject and aspirate rinsing fluid (typicallyin multiple cycles), and finally refill the reservoir 104 with new drug.This entire process is preferably carefully monitored by the controlcircuitry and/or the treating physician to facilitate proper adjustmentsof pump pressures and flow rates, valve settings, etc. and detect anyproblems. For this purpose, the refill system 300 (including the refilltool) and/or the drug pump device 100 may be equipped with flow,pressure, and other sensors. For example, during the fill process, thepressure inside the drug reservoir 104 alternates between a negativevalue (while material is vacuumed out) and a positive value (while drugis being introduced). One or more pressure sensors integrated in thedrug reservoir and/or the refill port can be employed to monitor thisprocess and ensure proper operation as well as reservoir integrity. Forexample, if certain expected pressure levels are not reached, this mayindicate a leak in the reservoir or elsewhere. Sensor feedback mayimmediately be provided to the refill system 300 via the wirelesstelemetry link. Pressure sensors may also be placed into the refillpumps 314. If the pressure detected in the reservoir 104 matches thatapplied by the pump of the refill system 300, successful refill isensured. Flow sensors may be integrated, for example, into the refillneedle, the channels connecting the needle to the cartridges, and therefill port, and may serve to keep injection rates within safe limits.Furthermore, a vision-based (e.g., camera) system may be employed totrack the drug pump device 100 and the site where it is implanted (e.g.,the patient's eye) during refill. The drug reservoir 104 may alsoinclude chemical sensors for monitoring drug potency, and/or viscositysensors that detect if the drug denatures and changes in structure. Thevarious sensors may also serve to monitor reservoir integrity outsidethe refill process. Problems can be inferred, for example, from anysudden change in pressure, viscosity, or chemical characteristics.

In various embodiments, the drug reservoir 104 of the pump is formedfrom a collapsible membrane and is covered with a hard outer shell 116,which protects the reservoir 104 from accidental compression by bodytissues or outside forces. The drug is forced out of the reservoir 104under pressure from a separate electrolysis chamber 106, which isexpanded via hydrolysis. After each active dosing cycle, hydrolysis endsand the electrolyte returns to a liquid state. The contents of drugreservoir 104 are reduced by the amount of drug dosed during that cycle,and so the combined volume of the drug reservoir 104 and deflatedelectrolyte chamber 106 is smaller after each dosing cycle. If the drugreservoir and electrolyte chamber were contained within a fixed-volumeshell 116, a vacuum would develop which would then need to be overcomewith additional hydrolysis each cycle.

A large hole in the hard shell is one solution to allowing fluid to flowin under the hard shell to balance the negative pressure created by thediminishing drug reservoir. Upon completion of the drug-dosing cycle,bodily fluid is drawn in through the hole to replace the drug ejectedfrom the reservoir. With a sufficiently large hole, upon the next cycleof dosing this bodily fluid is forced back out, and thus the electrolytechamber must be inflated past the previous volume in order to dose newdrug from the reservoir. This design is progressively inefficient, asthe expansion required of the electrolyte chamber increases withdecreasing volume of drug remaining in the drug reservoir.

If the pump is implanted such that the drug reservoir is full for a longenough time that tissue encapsulation around the implant fully develops,and is stable, then the encapsulation overlying the hole in the hardshell may act as a biological valve, allowing out-flow of fluid butserving as a “leaky” check-valve that prevents the free flow of fluidback into the space under the hard shell. Fluid can be expected to passslowly under these circumstances, balancing the depleted volume of thedrug reservoir.

Assuming the hole is sized to prevent growth of tissue in and under thehard shell, difficulties may be encountered during evacuation, flushingand refill of the drug reservoir. In these circumstances,pressure-balancing fluid from the body will only slowly enter under thehard shell (due to the valve effect of the overlying tissue), greatlyincreasing the amount of time a drug removal/flush/refill cycle cantake. In this case, it is desirable to balance pressure when attemptingto remove fluid from the drug reservoir.

One way to provide a volumetric offset to allow removal of fluid fromthe drug reservoir relies on the pump's electrolyte readily vaporizingunder negative pressure. If the electrolyte gasses under mild negativepressure, and the hard shell is sufficiently strong to withstandnegative pressure, then suction placed on the refill port will easilyremove fluid from the drug reservoir, as the electrolyte chamberinflates under the resulting negative pressure. The tube for conductingfluid between the drug reservoir and the refill port will besufficiently strong to withstand negative pressure without collapse.

In this case, inflating and deflating the drug reservoir during removalof unused drug, the inflow of flushing fluid, removal of flushing fluidand the final inflow of new medication is balanced by the phaseconversion of the electrolyte to and from the gaseous state. If theelectrolyte is chosen appropriately, this process occurs quickly andwith only minimal negative pressure exerted on the system. If the freeflow of fluid out from under the hard shell must be restricted, however(e.g., by the use of very small holes or a semi-permeable membrane),then the foregoing approach may not allow enough time for the fluid tobe forced out prior to refill. In particular, removal of body fluidthrough the small holes or membrane in the hard shell may take too longto be performed during the refill procedure with a needle residing inthe refill port.

In this case, the pump may be activated in a “re-establish volume” modewhereby the dosing rate is set extremely low, or else the pump may beoperated in a sub-pumping pressure mode such that the bodily fluid isforced out through the hard shell over an extended period of time, priorto refill. Using the pump electrolyte to balance pressures during therefill procedure presumes an electrolyte chamber that can fully inflateto nearly the entire volume under the hard shell. One way to balancenegative pressure resulting from removal of fluid from the drugreservoir is to activate the pump in a very low dosing mode orsub-pumping pressure mode such that the electrolyte chamber is inflatedas drug exits the drug reservoir. In effect, the inflating electrolytechamber is used to balance negative pressure created by withdrawal offluid from the drug reservoir. Fluid injected into the drug reservoirpressurizes the electrolyte chamber, forcing the electrolyte back into aliquid state. The electrolyte is chosen to return to a liquid state in areasonable amount of time in order to minimize the time necessary forthe refill procedure.

Alternatively, the pump itself may actively force fluid out of the drugreservoir by inflating the electrolyte chamber to pressurize the drugreservoir, forcing drug from the reservoir through a needle insertedinto the refill chamber, with the refill device remaining passive duringwithdrawal of fluid. A needle is inserted prior to inflating theelectrolyte chamber, or the pump is operated in a sub-pumping pressuremode (where the pressure developed on the electrolyte and drugreservoirs is below that of the cannula check valve to prevent dosing).

If a port is provided directly to the outer chamber where bodily fluidaccumulates under the hard shell, then withdrawal of unused drug fromthe reservoir, flushing and replenishment with new drug can be achievedquickly and easily therethrough—i.e., this port permits the free flow ofpressure-balancing fluid throughout the procedure, facilitating itsrapid completion. But in order to retain the added efficiency thatresults from restricting the movement of the fluid in the outer chamber,a reliable septum should also be included in this port in order toprevent fluid from escaping the outer chamber during drug dosing. Ifsuch a fluid-flow restriction is not desired or needed, the additionalport can be structurally simple, and the septum need only prevent tissuefrom growing in and obstructing access.

An additional port to allow fluid flow in and out of the outer chamberunder the hard shell requires its own needle. Any of a variety ofconfigurations can accommodate this requirement. In one implementation,the outer chamber has an entirely separate access port area into which asmall butterfly needle is inserted. This needle may contain a smallamount of saline in a collapsible reservoir, allowing it to remainpassively in place throughout the procedure, with fluid flowing in andout of the needle reservoir while the refill system operates. Thesequence is as follows: (1) when the refill system withdraws remainingunused drug from drug reservoir, saline flows into the outer chamberfrom the second needle to match the aspirated volume; (2) when flushingfluid is injected into the drug reservoir, saline flows out of the outerchamber into the second needle reservoir, (3) when the flushing fluid iswithdrawn from the drug reservoir, saline flows back into the outerchamber, and (4) when new drug is injected into drug reservoir, salineflows back into the second needle reservoir. After completion of thisprocess, both needles are removed.

The two needles, along with the waste/saline reservoir for the outerchamber, may also be incorporated into one refill device. For example,as illustrated in FIG. 8A, the two ports 124, 800 may be placedside-by-side such that both needles 106, 802 enter the pump device 100simultaneously. The two needles 106, 802 may, for example, havedifferent lengths and the two port septums 204, 804 may have differentthicknesses to prevent the needles from fully entering the wrong port.Active pump pressure sensing may also assist in detecting if the needlesare correctly placed in the ports.

Alternatively, a single, dual-septum port may be employed, as shown inFIG. 8B. For example, a communicating space 810 below the first septum812 may lead to the outer chamber, with the communicating space 814underneath the second septum 204 leading to the drug reservoir 104. Therefill device has two needles, one longer than the other, such that whenthe longer needle 816 is fully inserted into the dual-septum port (i.e.,into the lower communicating port), the shorter needle 818 resides inthe upper port. The two needles cannot being mistakenly interchanged,because the lower port would always communicate with one chamber of theimplant while the upper port could only communicate with the other. Whenproperly inserted, the two needles push and/or pull the unused drug,flushing fluid and replenishing drug as appropriate.

Having described certain embodiments of the invention, it will beapparent to those of ordinary skill in the art that other embodimentsincorporating the concepts disclosed herein may be used withoutdeparting from the spirit and scope of the invention. For example,various features described with respect to one particular device typeand configuration may be implemented in other types of devices andalternative device configurations as well. Accordingly, the describedembodiments are to be considered in all respects as only illustrativeand not restrictive.

What is claimed is:
 1. A combination comprising an implanted, refillabledrug pump device and an external system for filling the implanted,refillable drug pump device, the combination comprising: an implanted,refillable drug pump device comprising a memory and a drug reservoirwith a fill port; a needle for insertion into the fill port of theimplanted drug pump device; and an external refill system for refillingthe implanted pump device via the needle, the refill system comprising:at least one fluid container fluidly connectable to the needle and tothe drug reservoir therethrough; at least one pump for causing fluidflow through the needle between the at least one fluid container and thedrug reservoir; electronic circuitry including a processor forcontrolling operation of the at least one pump to perform a refilloperation; and a wireless communication module facilitating wirelessdata exchange between the electronic circuitry of the external refillsystem and the implanted drug pump device for wirelessly obtainingsensor data from sensors in the implanted drug pump and transmitting theobtained sensor data to the electronic circuitry, wherein the electroniccircuitry is configured to (i) determine refill information based on thesensor data and (ii) cause the wireless communication module to send thedetermined refill information to the implanted, refillable drug pumpdevice for storage in the memory thereof, wherein the refill informationcomprises at least one of a volume injected into the reservoir, a typeof drug, a drug dosing schedule, or a date of refill, and the electroniccircuitry is configured to perform the refill operation by controllingthe at least one pump based at least in part on the obtained sensordata, the refill information sent from the wireless communication moduleand stored in the memory, and a current fill level of the drugreservoir.
 2. The combination of claim 1, further comprising: tubing forfluidically connecting the at least one fluid container to the needle.3. The combination of claim 1, wherein the wireless communication moduleis integrated in the electronic circuitry.
 4. The combination of claim1, wherein the wireless communication module is integrated in a handheldtelemetry wand in communication with the electronic circuitry.
 5. Thecombination of claim 1, wherein the wireless communication module isintegrated in patient-worn eyeglasses in communication with theelectronic circuitry.
 6. The combination of claim 1, wherein the sensordata comprises sensor readings of sensors disposed in the drugreservoir.
 7. The combination of claim 1, wherein the wireless datacomprises information indicative of a type of drug to be administered.8. The combination of claim 1, wherein the wireless data comprisesinformation indicative of an error condition that has occurred in thedrug pump device since a previous communication between the electroniccircuitry and the drug pump device.
 9. The combination of claim 1,wherein the electronic circuitry is configured to control pump operationbased, at least in part, on sensor readings of at least one of flowsensors or pressure sensors disposed in at least one of the needle, theat least one pump, or a fluidic connection between the needle and the atleast one fluid container.
 10. The combination of claim 1, wherein thewireless communication module is configured to retrieve refillinformation previously sent from the external refill system and storedin the implanted drug pump device, the electronic circuitry beingconfigured to perform the refill operation by controlling the at leastone pump based at least in part on the retrieved refill information. 11.The combination of claim 9, wherein the refill information comprises atleast one of a type of drug, an amount of drug, a dosing schedule, or arefill date.
 12. The combination of claim 1, wherein the at least onefluid container comprises a drug-containing cartridge.
 13. Thecombination of claim 12, wherein the at least one fluid containerfurther comprises at least one of a waste-fluid receptacle or arinsing-fluid-containing cartridge.
 14. The combination of claim 12,wherein the drug-containing cartridge comprises a label indicative of atype of drug contained in the cartridge.
 15. The combination of claim14, wherein the label comprises at least one of a barcode, an RFID, anoptical ID, or an EPROM.
 16. The combination of claim 14, furthercomprising a reader for reading the label.
 17. The combination of claim14, wherein the electronic circuitry activates the at least one pump soas to cause fluid flow from the drug-containing cartridge to the drugreservoir only if the type of drug indicated by the label matches a typeof drug to be administered as determined based on data received from theimplanted drug pump device via the wireless communication module. 18.The combination of claim 12, wherein the drug-containing cartridge has ashape indicative of a type of drug contained in the cartridge.
 19. Thecombination of claim 1, wherein the electronic circuitry furtherfacilitates data exchange with an external server.
 20. The combinationof claim 19, wherein the data exchanged with the external servercomprises a serial number of the implanted drug pump device and dataassociated therewith, the serial number being received by the systemfrom the implanted drug pump device via the wireless communicationmodule.
 21. The combination of claim 20, wherein the data associatedwith the serial number of the implanted drug pump device comprises atleast one of patient data, a drug dosage log, or a drug pump devicehistory.
 22. A combination comprising an implanted, refillable drug pumpdevice and a system for filling the implanted, refillable drug pumpdevice, the combination comprising: an implanted, refillable drug pumpdevice comprising a memory and a drug reservoir with a fill port; a baseunit comprising (i) a pump for causing fluid flow through a fluidicconnection between a drug-containing cartridge and the drug reservoir,and (ii) electronic circuitry including a processor for controllingoperation of the pump; and in communication with the base unit, awireless communication module facilitating wireless data exchange withthe implanted, refillable drug pump device and configured to send drugdelivery protocols for storage in the memory of the implanted,refillable drug pump, the data including an identification of the drugin the cartridge, wherein the electronic circuitry of the base unit isconfigured to provide new programming to the implanted drug pump devicebased on the identification, if the identification does not match a drugthat the implanted, refillable drug pump device was previouslyprogrammed to accept, the new programming causing the implanted,refillable drug pump device to accept the drug in the cartridge,retrieve a new drug delivery protocol associated with the identificationfrom the drug delivery protocols sent from the wireless communicationmodule and stored in the memory, and execute the retrieved drug deliveryprotocol.
 23. A method of verifying proper selection of a drug prior toinjection thereof by a refill system into a drug reservoir of animplanted drug pump device, the method comprising the steps of:receiving a drug cartridge in a well of the refill system, the drugcartridge having an electronically readable label indicative of a drugcontained in the cartridge; causing the refill system to electronicallyread the label, causing the refill system to (i) receive, from theimplanted drug pump device via a wireless communication module of therefill system, data indicative of a drug to be administered and (ii)send drug delivery protocols to the implanted drug pump device, via thewireless communication module, for storage in a memory associated withthe implanted drug pump device, the data including an identification ofthe drug in the cartridge; and causing the refill system to determinewhether the drug indicated by the label matches the drug to beadministered, and in accordance with a determination that the drugindicated by the label does not match the drug to be administered, uponoperator command providing new programming to the implanted drug pumpdevice to cause the implanted drug device to accept the drug in thecartridge, retrieve a new drug delivery protocol associated with thedrug from the drug delivery protocols sent from the wirelesscommunication module and stored in the memory, and execute the retrieveddrug delivery protocol, and in accordance with a determination that thedrug indicated by the label matches the drug to be administered,injecting the drug into the reservoir.
 24. The combination of claim 22,wherein the wireless communication module is configured to send the newdrug-delivery protocol to the implanted drug pump device for storagetherein.
 25. The combination of claim 23, wherein the wirelesscommunication module is configured to send the new drug-deliveryprotocol to the implanted drug pump device for storage therein.
 26. Thecombination of claim 1, wherein the drug reservoir is collapsible. 27.The combination of claim 1, wherein the refill information furthercomprises at least one of a drug dosing log or an operating historycomprising information about an error condition that has occurred in theimplanted, refillable drug pump device.